Extracellular Matrix-Specific Platelet Activation Leads to a Differential Translational Response and Protein De Novo Synthesis in Human Platelets
Open Access
- 31 October 2020
- journal article
- research article
- Published by MDPI AG in International Journal of Molecular Sciences
- Vol. 21 (21), 8155
- https://doi.org/10.3390/ijms21218155
Abstract
Platelets are exposed to extracellular matrix (ECM) proteins like collagen and laminin and to fibrinogen during acute vascular events. However, beyond hemostasis, platelets have the important capacity to migrate on ECM surfaces, but the translational response of platelets to different extracellular matrix stimuli is still not fully characterized. Using 2D-gel electrophoresis, confocal microscopy, polysome analysis and protein sequencing by mass spectrometry, we demonstrate that platelets show a differential expression profile of newly synthesized proteins on laminin, collagen or fibrinogen. In this context, we observed a characteristic, ECM-dependent translocation phenotype of translation initiation factor eIF4E to the ribosomal site. eIF4E accumulated in polysomes with increased binding of mRNA and co-localization with vinculin, leading to de novo synthesis of important cytoskeletal regulator proteins. As the first study, we included a proteome analysis of laminin-adherent platelets and interestingly identified upregulation of essentially important proteins that mediate cytoskeletal regulation and mobility in platelets, such as filamin A, talin, vinculin, gelsolin, coronin or kindlin-3. In summary, we demonstrate that platelet activation with extracellular matrix proteins results in a distinct stimulus-specific translational response of platelets that will help to improve our understanding of the regulation of platelet mobility and migration.This publication has 43 references indexed in Scilit:
- High shear flow induces migration of adherent human plateletsPlatelets, 2011
- Filamin A regulates monocyte migration through Rho small GTPases during osteoclastogenesisJournal of Bone and Mineral Research, 2010
- Vinculin Nucleates Actin Polymerization and Modifies Actin Filament StructureOnline Journal of Public Health Informatics, 2009
- Protein synthesis by platelets: historical and new perspectivesJournal of Thrombosis and Haemostasis, 2009
- An Exocyst Complex Functions in Plant Cell Growth inArabidopsisand TobaccoTHE PLANT CELL ONLINE, 2008
- Signal-dependent splicing of tissue factor pre-mRNA modulates the thrombogenecity of human plateletsThe Journal of Experimental Medicine, 2006
- Regulating cell migration: calpains make the cutJournal of Cell Science, 2005
- Escaping the Nuclear Confines: Signal-Dependent Pre-mRNA Splicing in Anucleate PlateletsCell, 2005
- Human platelets exhibit chemotaxis using functional N-formyl peptide receptorsExperimental Hematology, 2005
- Activated platelets signal chemokine synthesis by human monocytes.JCI Insight, 1996